Functional and metabolic MRI techniques have been rapidly evolving and have tremendous potential for clinical brain disorders research. Clinical activation fMRI studies are performed at using blood oxygenation level dependent (BOLD) contrast method. Multiple Sclerosis patients and healthy controls were evaluated to determine the activation in the contralateral primary sensorimotor cortex and deactivation (mediated by transcallosal tracts) in the homologous ipsilateral region during a simple hand tapping task Both healthy controls and MS patients showed similar activation in the motor cortex contralateral to the hand moved, but the patients showed a significantly smaller relative deactivation in the ipsilateral motor cortex. The difference was accounted for by the sub-group of MS patients who previously had impairment of motor function of the hand tested. The corpus callosum (CC) of the whole patient group was significantly thinner than for the controls. Atrophy of the CC was correlated with loss of deactivation for the whole patient group, but particularly for MS patients. Interhemispheric physiological inhibition thus is impaired in patients with MS, potentially contributing to impairment of motor control. This work suggests one way in which FMRI monitoring of the transcallosal interactions in motor cortex could become a tool for evaluation of therapies that may enhance function in reversibly impaired pathways.